Label‐free Raman spectroscopy for the assessment of liver fibrosis

Abstract

The enormous incidence and dire consequences of liver fibrosis highlight the need for biologically plausible markers as readouts of pathology and drug efficacy. The classic reference standard for diagnosis of liver fibrosis is histopathological examinations. However, it is burdened by time‐consuming steps, subjectivity, and the static nature of information. Raman spectroscopy is a rapid, objective, and label‐free analytical tool that provides numerous molecular information. Thus, we utilized Raman spectroscopy to characterize the pathological features of liver fibrosis and to evaluate the efficacy of drugs (obeticholic acid [OCA] and gigantol [YS30]). Principal component analysis with subsequent linear discriminant analysis could basically discriminate between fibrotic mice and healthy controls and showed that animals with OCA or YS30 treatment resembled those with vehicle treatment. Moreover, we identified several potential biomarkers, including cytochrome C, for liver fibrosis development based on their Raman “fingerprints.” Raman imaging provided quantitative and spatial distribution of collagen and cytochrome C in situ. In addition, we demonstrated the role of OCA or YS30 in revitalizing mitochondrial function to alleviate liver fibrosis using Raman spectroscopy. Collectively, Raman spectroscopy succeeded in tracking liver fibrosis progression, assessing drug efficacy, and yielding significant molecular information useful for quantitatively linking pathological assessment and mechanism of drug action.

Innovative Approaches for Drug Discovery: Quantifying Drug Distribution and Response with Raman Imaging

“…148 Cao et al applied RS to assess the efficacy of obeticholic acid and gigantol for treating liver fibrosis. 149 Li et al monitored drug-induced cytotoxicity and detected cytotoxicity earlier than MTT assay with RS. 150 Despite the potential demonstrated by these studies, as mentioned earlier, RS is hindered by slow image acquisition speeds rendering large data sets difficult to acquire.…”

“…Yay et al used RS to analyze kidney tissue damage by antioxidants and cisplatin . Cao et al applied RS to assess the efficacy of obeticholic acid and gigantol for treating liver fibrosis . Li et al monitored drug-induced cytotoxicity and detected cytotoxicity earlier than MTT assay with RS …”